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Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Justification for grouping of substances and read-across

There are no reliable data available on skin sensitisation for Glycerides, mixed C8-C10 and succinyl (CAS 91744-56-8). In order to fulfil the standard information requirements set out in Annex VII, 8.3, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006, read-across from structurally related substances is conducted.

In accordance with Article 13 (1) of Regulation (EC) No 1907/2006, "information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI are met.” In particular for human toxicity, information shall be generated whenever possible by means other than vertebrate animal tests, which includes the use of information from structurally related substances (grouping or read-across).

Having regard to the general rules for grouping of substances and read-across approach laid down in Annex XI, Item 1.5, of Regulation (EC) No 1907/2006, whereby physicochemical, toxicological and ecotoxicological properties may be predicted from data for reference substance(s) by interpolation to other substances on the basis of structural similarity, Glycerides, mixed decanoyl and octanoyl (73398-61-5) and succinic acid (CAS 110-15-6) are selected as reference substances for assessment of the skin sensitising potential of Glycerides, mixed C8-C10 and succinyl.

The read-across is based on structural similarity between the source and target substances, as the substance Glycerides, mixed C8-C10 and succinyl is composed of esters of glycerol with succinic acid and fatty acids with carbon chain lengths of C8 and C10. A detailed analogue approach justification is provided in the technical dossier (see IUCLID Section 13).

Overview of skin sensitisation

CAS#

91744-56-8 (a)

73398-61-5 (b)

110-15-6

Chemical name

Glycerides, mixed C8-C10 and succinyl

Glycerides, mixed decanoyl and octanoyl

Succinic acid

Molecular weight (range)

470.68-1211.64

470.69-554.85

118.09

Skin sensitisation

WoE

Experimental result:

inconclusive

RA: CAS 73398-61-5

RA: CAS 110-15-6

Experimental result:

not sensitising in humans

Experimental result:

not sensitising

(a) The substance subject to the REACh Phase-in registration deadline of 31 May 2013 is indicated in bold font. Only for this substance a full set of experimental results and/or read-across is given.

(b) Reference (read-across) substances are indicated in normal font. Lack of data for a given endpoint is indicated by “--“.

 

Skin sensitisation

CAS No. 91744-56-8

The substance Glycerides, mixed C8-C10 and succinyl was tested for the induction of skin sensitisation in an early study conducted according to the method described by Magnusson and Kligman (1969). Ten male guinea pigs were induced by intradermal injections of the undiluted test material, the test material in Freund’s adjuvant (50% v/v) and Freund’s adjuvant alone. Seven days after injections, the animals were epicutaneously induced by exposure to the undiluted test material for 48 h under occlusive conditions. Animals were challenged 2 weeks thereafter by occluded topical application of the undiluted test material for a period of 24 h. Skin reactions were evaluated 24 and 48 h after patch removal (i.e. 48 and 72 h after challenge application). No discernible dermal reactions were observed at the two post-challenge readings, and in was therefore concluded that no evidence of contact sensitisation was found in the test population. However, since no controls (negative and positive) were included in the study, the results are regarded as inconclusive.

CAS No. 73398-61-5

The substance Triglycerides, mixed decanoyl and octanoyl was tested for its skin sensitisation potential in a human Repeated Insult Patch Test (Eisenberg, 1996). 54 volunteers were induced epicutaneously (interscapular back skin) with 0.2 mL of the unchanged test substance for an exposure period of 24 h under semi-occlusive conditions. Inductions were performed three times a week for a total of ten applications. The challenge application was performed two weeks after the last induction on the volar forearm. Skin reactions were observed 24 and 48 h after challenge application on the volar forearm. None of the 54 tested volunteers showed any skin reactions, indicating that the test material was not skin sensitising to human skin under the conditions of this study.

CAS No. 110-15-6

In a study by Kreiling et al. (2008), a comparison of the skin sensitising potential of succinic acid as assed by the murine Local Lymph Node Assay (LLNA) and the Guinea Pig Maximisation Test (GPMT) was conducted. Both tests were conducted according to the corresponding OECD guideline (429 and 406, respectively) and under GLP conditions.

In the LLNA, Groups of 5 female mice per concentration level were treated with 50 µL (25 µL per ear) of the vehicle (DMSO) or the test material at 5, 10 and 25% for 3 consecutive days. Five days after the first application, animals were injected with ³H-methylthymidine (³HTdR) at 20 µCi/mouse. The draining auricular lymph nodes (left and right) from all mice were excised 5 h after injection and pooled for each animal. Single cell suspensions of pooled lymph node cells were prepared for determination of ³HTdR incorporation by β-scintillation counting. The proliferation response of lymph node cells was expressed as the number of radioactive disintegrations per minute per lymph node (DPM/node) and as the ratio of ³HTdR incorporation into lymph node cells of test nodes relative to that recorded for the control nodes (Stimulation Index, SI).

No signs of systemic toxic effects were observed. No clinical signs of local irritation were observed by visual inspection of the ears. Similarly, no significant ear swelling and no increases in the mean lymph node weight relative to control was measured at any of the test concentrations.

The stimulation index values of the test substance were 1.3, 1.2 and 1.2 at treatment concentrations of 25%, 10% and 5%, respectively. No significant dose-response relationship was observed. Based on the results, EC3 values were not calculated. The test material was thus considered to be not sensitising under the conditions of the test.

In the GPMT, ten female guinea pigs were induced by intradermal injections of the test material at 0.5% in cottonseed oil, the test material (0.5%) in Freund’s adjuvant (50% v/v) and Freund’s adjuvant alone. One week later, the animals were induced by epicutaneous exposure to the test material (25% in Vaseline) for 48 h under occlusive conditions. Animals were challenged and re-challenged 2 and 3 weeks thereafter, respectively, by occluded topical application of the test material (10% in Vaseline) for a period of 24 h. Skin reactions were evaluated 24, 48 and 72 h after patch removal (i.e. 48, 72 and 96 h after challenge application). No signs of systemic toxicity were observed. In 2 animals of the treatment group, skin reactions were only seen at 24 or 72 h after patch removal, respectively. Moreover, 1 control animal showed a skin reaction of the same grade (grade 1) at 24 h, but not at the other reading time points. After re-challenge, neither of the 2 animals of the treatment group displayed a skin reaction. Thus, it can be concluded that positive reactions in these animals (as well as those in the control group) were not caused by a specific immune reaction. Undecylenic acid was not designated as positive control. However, it may be used to demonstrate the sensitivity and reliability of the test, since it provoked > 30% positive skin reactions (in 4/10 animals) after both challenge exposures. Under the conditions of this study, the test substance was considered to be not sensitising.

Conclusions for skin sensitisation

Glycerides, mixed C8-C10 and succinyl has been tested for skin sensitisation in a Guinea Pig Maximisation Test. No skin reactions were observed after induction and challenge application of the test substance at 100%. However, due to the lack of concurrent negative and positive control data, the result is considered inconclusive.

Therefore, hazard assessment is conducted by means of read-across and in a weight of evidence approach taking into account available data for esters of glycerol with C8 and/or C10 acids as well as for succinic acid.

The substance Glycerides, mixed decanoyl and octanoyl (73398-61-5) has been tested for skin sensitisation in humans, while animal data are available for succinic acid (CAS 110-15-6). The available studies show that both substances are not skin sensitising.

Overall, the available data provide sufficient weight of evidence leading to the conclusion that the substance Glycerides, mixed C8-C10 and succinyl is not sensitising to the skin.

Migrated from Short description of key information:

Based on weight of evidence from substance specific data and read-across from structurally similar substances (glycerides and succinic acid):

Skin sensitisation: not sensitising

Justification for selection of skin sensitisation endpoint:

Hazard assessment is conducted by means of read-across from structural analogues/surrogates. All available studies are adequate and reliable based on the identified similarities in structure and intrinsic properties between source and target substances and overall quality assessment (refer to the endpoint discussion for further details).

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on substance specific studies and read-across from structural analogues, the available data on the skin sensitising potential of Glycerides, mixed C8-C10 and succinyl do not meet the classification criteria according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.

There are no data available on respiratory sensitisation.

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